Reductions in both the size of the amygdala and functional activity during emotional processing have been independently associated with trauma exposure and severity, raising the question of whether reduced volume prompts reduced functional activation. In this multimodal assessment, the relationship between amygdala structure and function was investigated in mood and anxiety patients to determine their covariation and their relationship to trauma magnitude. Overall, amygdala volume and functional emotional reactivity were unrelated, with smaller volumes and reduced emotional reactivity each independently predicting trauma magnitude for women, and mediation analysis did not support a hypothesis that the relationship between reduced functional activity and trauma severity depends on amygdala volume. Structural and functional differences were instead separately related to different facets of trauma experience, highlighting the need for longitudinal and multimodal analyses to further elucidate the relationship between brain structure, function, and psychopathology.

Identification of previous SARS-CoV-2 infection typically relies on serology, yet T-cells play a key role in the adaptive immune response against SARS-CoV-2. Here, we investigated in parallel the SARS-CoV-2-specific as well as endemic human coronavirus-specific humoral and cross-reactive cellular responses in children and adults. We analyzed clinical data and blood samples from a family cohort of 96 children and 144 adults at 3-4 and 11-12 months after their first contact with SARS-CoV-2. Humoral response was assessed by a multiplex immunoassay with high sensitivity and specificity (MULTICOV-AB). Cellular responses were analyzed by IFN-γ ELISPOT using four different established epitope compositions (ECs) to discriminate between SARS-CoV-2 specific and HCoV cross-reactive T-cell responses. While the majority of adults had a combined serological and T-cell response, relatively more children had a T-cell response alone rather than a combined response. The magnitude of the T-cell response correlated with symptoms and the humoral response. In addition, SARS-CoV-2 infection significantly boosted the endemic coronavirus-specific cellular response. Overall, our data suggest discordant humoral and cellular responses, reflecting either abortive infection, cellular sensitization with rapid viral clearance or rapid antibody waning or a combination of these phenomena. Restricting epidemiologic analysis to SARS-CoV-2 serological data may underestimate rates of infection with or at least exposure to SARS-CoV-2 in children.

Allogeneic hematopoietic stem cell transplantation (HSCT) serves as a therapeutic intervention for various pediatric diseases. Acute kidney injury afflicts 21-84% of pediatric HSCT cases, significantly compromising clinical outcomes. This retrospective single-institution analysis scrutinized the practice of substituting nephrotoxic ciclosporin A with the everolimus/mycophenolate mofetil combination as graft-versus-host disease (GVHD) prophylaxis in 57 patients following first allogeneic matched donor HSCT. The control cohort comprised 74 patients not receiving everolimus during the same timeframe. Study endpoints encompassed the emergence of retention parameters subsequent to the switch to everolimus, overall survival, relapse incidence of the underlying disease and acute and chronic GVHD in both treatment groups. Our findings reveal a significant improvement in renal function, evidenced by reduced creatinine and cystatin C levels 14 days after ceasing ciclosporin A and initiating everolimus treatment. Crucially, the transition to everolimus did not adversely affect overall survival post-HSCT (HR 1.4; 95% CI: 0.64 – 3.1; p=0.39). Comparable incidences of grade 2-4 and grade 3-4 acute GVHD as well as severe chronic GVHD were observed in both groups. Patients with an underlying malignant disease exhibited similar event-free survival in both treatment arms (HR 0.87, 95% CI: 0.39 – 1.9, p=0.73). This study provides compelling real-world clinical evidence supporting the feasibility of replacing CsA with everolimus and for the use of the everolimus/mycophenolate mofetil combination to manage acute kidney injury following HSCT in children. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study did not receive any funding. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was ethically approved by the institutional review board, Charite's Ethics Committee, under the reference EA2/144/15. This study adheres to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) principles. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.

BACKGROUND:Reactivation of viral infections, in particular cytomegalovirus (CMV) and adenovirus (ADV), cause morbidity and non-relapse-mortality in states of immune deficiency, especially after allogeneic hematopoietic cell transplantation (allo-HCT). Against the background of few available pharmacologic antiviral agents, limited by toxicities and resistance, adoptive transfer of virus-specific T-cells (VST) is a promising therapeutic approach. METHODS:We conducted a single-center retrospective analysis of adult patients treated with ADV- or CMV-specific T-cells in 2012-2022. Information was retrieved by review of electronic health records. Primary outcome was a response to VST by decreasing viral load or clinical improvement. Secondary outcomes included overall survival and safety of VST infusion, in particular association with graft-versus-host disease (GVHD). RESULTS:Ten patients were included, of whom four were treated for ADV, five for CMV, and one for ADV-CMV-coinfection. Cells were derived from stem cell donors (6/10) or third-party donors (4/10). Response criteria were met by six of 10 patients (4/4 ADV, 2/5 CMV, and 0/1 ADV-CMV). Overall survival was 40%. No infusion related adverse events were documented. Aggravation of GVHD after adoptive immunotherapy was observed in two cases, however in temporal association with a conventional donor lymphocyte infusion and a stem cell boost, respectively. CONCLUSION:In this cohort, CMV- and ADV-specific T-cell therapy appear to be safe and effective. We describe the first reported case of virus-specific T-cell therapy for CMV reactivation not associated with transplantation but with advanced HIV infection. This encourages further evaluation of adoptive immunotherapy beyond the context of allo-HCT.

Background: Exagamglogene autotemcel (exa-cel) is a non-viral cell therapy designed to reactivate fetal hemoglobin (HbF) via ex vivo CRISPR-Cas9 gene-editing of autologous CD34+ hematopoietic stem and progenitor cells (HSPCs) at the erythroid-specific enhancer region of BCL11A in patients (pts) with transfusion-dependent β-thalassemia (TDT). Here we report that in a pre-specified interim analysis, the pivotal CLIMB THAL-111 trial of exa-cel met primary and key secondary endpoints. Methods: CLIMB THAL-111 is an ongoing, 24-month (mo), phase 3 trial of exa-cel in pts age 12-35y with TDT and a history of ≥100 mL/kg/y or ≥10 U/y packed red blood cell (RBC) transfusions in the 2y before screening. Primary endpoint is transfusion independence defined as proportion of pts maintaining a weighted average hemoglobin (Hb) ≥9 g/dL without RBC transfusion for ≥12 consecutive mos (TI12). Key secondary endpoint is proportion of pts maintaining a weighted average Hb ≥9 g/dL without RBC transfusion for ≥6 consecutive mos (TI6). Evaluable pts had ≥16 mos of follow-up after exa-cel infusion. Evaluation of TI12 and TI6 started 60 days after last RBC transfusion for post-transplant support or TDT management. Pts completing trial enrolled in long-term follow-up Study 131. Mean (SD) shown except where noted. Results: As of 16 Jan 2023, 52 pts (mean age 21.5[range 12-35]y; 18[34.6%] age ≥12 to <18y; 31[59.6%] with severe genotypes [β 0/β 0 or β 0/β 0-like], median annualized transfusion volume 201.0 mL/kg) received exa-cel; median follow-up 20.4 (range 2.1-48.1) mos. Following infusion, all pts engrafted neutrophils and platelets (median 29 and 44 days, respectively). Of the 35 pts evaluable for primary and key secondary endpoints, 32 (91.4%) achieved TI12 and TI6 (95% CI: 76.9%, 98.2%; P<0.0001). Pts achieving TI12 stopped transfusions 35.2 (SD, 18.5) days after exa-cel infusion and remained transfusion independent for 22.5 (range, 13.3, 45.1) mos (Fig). For 3 pts not achieving TI12, one had reductions in annualized RBC transfusion volume of 83.9%, while the others have been transfusion-free for 7.3 mos and 4.0 mos starting 60 days after the last transfusion. For all pts, total Hb was 11.4 g/dL at Month 3 (≥12g/dL Month 6 onward) and HbF was 7.7 g/dL at Month 3 (≥ 10 g/dL Month 6 onward) with pancellular distribution (≥95% RBCs expressing HbF Month 6 onward). Proportion of edited BCL11A alleles was stable over time in bone marrow CD34 + and peripheral blood nucleated cells. Pts not yet evaluable and with sufficient follow-up were also transfusion-free. Quality-of-life (QOL) measures showed clinically significant improvements. All pts had ≥1 adverse event (AE), most were Grade 1 or 2; 46 (88.5%) pts had AEs of Grade 3 or 4 severity. Most common AEs were febrile neutropenia (61.5%), headache (53.8%), and stomatitis (50.0%). Most AEs and serious AEs (SAEs) occurred within first 6 mos after infusion. Two pts had SAEs considered related to exa-cel: headache, hemophagocytic lymphohistiocytosis (HLH), acute respiratory distress syndrome and idiopathic pneumonia syndrome (latter also considered related to busulfan) all in the context of HLH (n=1) and delayed engraftment and thrombocytopenia (both also considered related to busulfan) (n=1), which all resolved. There were no deaths, discontinuations, or malignancies. Conclusions: The CLIMB THAL-111 trial met primary and key secondary endpoints, with exa-cel treatment resulting in early and sustained increases in Hb and HbF leading to transfusion independence in >90% of pts with TDT and improved QOL. Safety profile of exa-cel was generally consistent with myeloablative busulfan conditioning and autologous transplantation. These results show exa-cel has the potential to deliver a one-time functional cure to pts with TDT.

ABSTRACT:Anti-T lymphocyte globulin (ATLG) significantly reduces the risk of engraftment failure in allogeneic hematopoietic stem cell transplant (HSCT) but hampers posttransplant immune reconstitution. We hypothesized that in patients receiving haploidentical CD3/CD19-depleted grafts, these double-edged effects could be better balanced by attaining high ATLG serum concentrations before transplant but as low as possible on the day of transplant. Therefore, we moved the start of ATLG application to day -12 and determined serum concentrations of T-cell-specific ATLG in pediatric patients treated with 3 established dosing regimens (15, 30, or 60 mg/kg). Corresponding mean T-cell-specific ATLG serum concentrations at day 0 were 1.14, 2.99, or 12.10 μg/mL, respectively. Higher ATLG doses correlated with higher peak levels at days -8 and -7 and reduced graft rejection, whereas lower ATLG doses correlated with significantly faster posttransplant recovery of T and natural killer cells. The rate of graft-versus-host disease remained low, independent of ATLG doses. Moreover, in vitro assays showed that ATLG concentrations of 2.0 μg/mL and lower only slightly reduced the activity of natural killer cells, and therefore, the function of such effector cells might be preserved in the grafts. Pharmacokinetic analysis, compatible with linear first-order kinetics, revealed similar half-life values, independent of ATLG doses. Hence, the day on which a desired ATLG serum level is reached can be calculated before HSCT. Our retrospective study demonstrates the relevance of dosing and time of administration of ATLG on engraftment and immune recovery in ex vivo CD3/CD19-depleted haploidentical HSCT.

The pivotal role of the cell entry receptor ACE2 for SARS-CoV-2 infection is well-established. When ACE2 is shed from cell surface into plasma as soluble ACE2 (sACE2), it can effectively neutralize SARS-CoV-2. This longitudinal prospective cohort study analyzed sACE2 activity in 1192 participants, aged 4 months to 81 years, 3 and 12 months after SARS-CoV-2 household exposure. Following SARS-CoV-2 exposure, participants exhibited significantly elevated sACE2 activity, irrespective of confirmed infection, with the highest levels observed in exposed children. Longitudinal analysis revealed a decline in sACE2 levels over time, reaching levels comparable to age- and sex-matched pre-pandemic controls. An increase in sACE2 activity was also confirmed in vitro in Calu-3 (human lung) cells within hours of SARS-CoV-2 exposure, providing a direct link between SARS-CoV-2 exposure and elevated sACE2. This study, therefore, challenges the dichotomy of categorizing SARS-CoV-2 exposed participants as infected or not infected solely on currently established diagnostic assays. It demonstrates lasting host responses independent of B- and T-cell memory and may help to keep SARS-CoV-2 infections in balance and contribute to successful virus clearance in children and adults lacking humoral and cellular immune responses following SARS-CoV-2 exposure.Trial Registration: German Registry for Clinical Studies; Identifier: D 00021521.

Second allogeneic stem cell transplantation can rescue a significant proportion of

Objective: Hematopoietic stem cell transplantation (HSCT) is highly distressing and potentially traumatizing for pediatric and young adult patients (PYAP). At present, there is little evidence on their individual burdens.Methods: In this prospective cohort study, the course of the psychological and somatic distress was investigated on eight observation days (day -8/-12,-5, 0 (day of HSCT), +10, +20, and + 30 before/after HSCT), using the PO-Bado external rating scale and the EORTC-QLQ-C15-PAL self-assessment questionnaire. Stress-associated blood parameters were determined and correlated with the results of the questionnaires.Results: A total of 64 PYAP with a median age of 9.1 years (range 0-26 years) who underwent autologous (n = 20; 31%; autoHSCT) or allogeneic (n = 44; 69%; alloHSCT) HSCT were analyzed. Both were associated with a significant reduction in QOL. The reduction in self-assessed QOL correlated with somatic and psychological distress as assessed by medical staff. While somatic distress was similar in both groups with a maximum around day+10 (alloHSCT 8.9 +/- 2.4 vs. autoHSCT 9.1 +/- 2.6; p = 0.69), a significantly higher level of psychological distress was seen during alloHSCT (e.g. day0 alloHSCT 5.3 +/- 2.6 vs. day0 autoHSCT 3.2 +/- 1.0; p < 0.0001).Conclusions: The maximum of psychological and somatic distress, as well as the lowest quality of life, ranges between day 0 and + 10 after both allogeneic and autologous pediatric HSCT. While somatic distress is similar during autologous and allogeneic HSCT, the allogeneic group seems to be affected by higher psychological distress. Larger prospective studies are needed to evaluate this observation.

Veno-occlusive disease (VOD) is a serious complication of hematopoietic stem cell transplantation (HSCT) with a high incidence in pediatric patients. This study aimed to detect signs of hypofibrinolysis using thrombelastography. In this prospective single-center study, thrombelastographic measurements (EX and TPA tests) were taken during HSCT to detect signs of impaired coagulation, clot formation, or hypofibrinolysis. Of 51 patients undergoing allogeneic and autologous HSCT, five (9.8

Despite highly intensive multimodality treatment regimens, the prognosis of patients with high-risk neuroblastoma (HRNB) and central nervous system (CNS) relapse remains poor. We retrospectively reviewed data from 13 patients with HRNB and CNS relapse who received multimodal therapy with consolidating haploidentical stem cell transplantation (haplo-SCT) followed by dinutuximab beta ± subcutaneous interleukin-2 (scIL-2). Following individual relapse treatment, patients aged 1−21 years underwent haplo-SCT with T/B-cell-depleted grafts followed by dinutuximab beta 20 mg/m2/day × 5 days for 5–6 cycles. If a response was demonstrated after cycle 5 or 6, patients received up to nine treatment cycles. After haplo-SCT, eight patients had a complete response, four had a partial response, and one had a stable disease. All 13 patients received ≥3 cycles of immunotherapy. At the end of the follow-up, 9/13 patients (66.7%) demonstrated complete response. As of July 2023, all nine patients remain disease-free, with a median follow-up time of 5.1 years since relapse. Estimated 5-year event-free and overall survival rates were 55.5% and 65.27%, respectively. Dinutuximab beta ± scIL-2 following haplo-SCT is a promising treatment option with a generally well-tolerated safety profile for patients with HRNB and CNS relapse.

Reduced hippocampal and/or amygdala volumes have been reported in patients with a variety of different anxiety diagnoses, suggesting that structural alterations may vary transdiagnostically across the internalizing disorders. The current study measured hippocampal and amygdala volumes in anxiety and mood disorder patients assessing differences that vary dimensionally with transdiagnostic factors of distress, anxious arousal, and trauma, based on a principal components analysis of questionnaires relating to symptomology. High-resolution structural images were collected in a sample of 165 patients, and volumes extracted from the hippocampal formation (including CA1, CA2/3, CA4/DG, subiculum, and molecular layer) and the amygdala. Transdiagnostically, increasing distress was associated with reduced hippocampal CA1 volume, increasing anxious arousal was associated with reduced hippocampal CA4/DG volume, and increasing trauma severity was associated with reduced amygdala volume in women. Taken together, the data indicate that subcortical brain volumes decrease as the severity of transdiagnostic psychopathological symptomology increases.

P Glogowski and L Thérond contributed equally to this work. Background Pediatric patients receive physiotherapy support during hematopoietic stem cell transplantation (HSCT) to prevent the deterioration of condition and musculature and to promote rehabilitation. Despite the good arguments in favor of physiotherapy, children often do not enjoy the exercises, or even refuse to participate. In our prospective study we show that our unique training program on the trampoline is convincing and superior to the standard physical therapy during HSCT. Patients and Methods In this monocentric, randomized, prospective study of the University Children's Hospital Tübingen, 52 HSCT patients between 5 and 22 years of age were followed during the in-patient stay in the context of HSCT, as well as in the post-transplant period until day +200 after HSCT. The therapy group (TG; n=26; TG) received a specially created exercise program five days a week with elements of strength and endurance training using a trampoline and an exercise ball. The TG was compared with a control group (CG; n=26) that received standard physical therapy. After in-patient discharge, TG patients were given an exercise plan and an exercise diary to complete independently at home. On six predefined approximate observation days (baseline: day of in-patient admission before HSCT, between day +3 to +8 after leukocyte/granulocyte “take”, after HSCT, day +60, day +100, day +150, and day +200 after HSCT), patients in both groups were assessed for muscle strength (full-ball bump, triple hop), stamina and endurance (timed-up-and-go, 6-minute walking), muscle development (muscle circumferences of M. triceps surae and M. quadriceps), emotional state and quality of life (questionnaires: SAM, KINDL-Onco-module). Data from the training tests, as well as from the questionnaires was used to fit linear mixed models. The equation used to fit the models can be described by DV ijk = β 0j + β 1j * day k + ϑ 0i + ϑ 1i + ε ijk. In this model equation DV ijk denotes the dependent variable of patient i = 1, ..., 52, in group j = 1 (CG) or 2 (TG), at day k = -53, ..., 367 after HSCT. β 0j and β 1j denote the fixed effects where β 0j is the intercept estimate (i.e. the dependent variable at day 0 after HSCT) and β 1j is the slope estimate (i.e. how much the dependent variable decreases or increases each day) for the respective group j. ϑ 0i and ϑ 1i describe the individual specific random intercept and slopes, while ε ijk is the error term. Results A total of 52 patients with a median age of 9.8 years (range 5.2 to 20.3 years), 29 of whom were females (55.8%), were included in this study. Of the patients, 45 (86.5%) and 7 (13.5%) underwent allogeneic or autologous HSCT, respectively. The underlying diseases were malignant in 63.5% of the cases (e.g., acute lymphoblastic leukemia, acute myeloid leukemia, neuroblastoma) and non-malignant in 36.5% of the cases (e.g., beta-thalassemia, sickle cell disease). The granulocyte and leukocyte take were each reached at a median of day +17 (range day +8 to day +30). The estimated fixed effects of the slopes of the analyzed data for the training tests and questionnaires can be found in the table. In the TG, there was a significant increase in the results of the walking test, the triple hop, the full ball bump, and triceps and quadriceps circumferences. No significant improvement over time was found in the CG. Looking at the difference between groups, the improvement in the TG was significantly greater for the walking test, the triple hop, and the quadriceps circumferences. For the questionnaire data, it was shown that both the CG and the TG had a significant decrease in debilitating physical, as well as debilitating psychological symptoms over time (KINDL body and KINDL mind). There was no significant difference between groups in these scales. For self-reported anxiety (SAM) and illness-related worries (KINDL disease) there was a significant decrease, while the scales KINDL friends and KINDL school increased significantly in the TG but not in the CG. For anxiety and the KINDL school scale this improvement was significantly greater in the TG than in the CG. Conclusions Our unique and new trampoline-based exercise program was able to counter standard physical therapy with significant improvements in muscle strength, endurance, as well as a reduction in anxiety and worry and an improved quality of life for the patients. And most importantly, our patients had an incredible amount of fun doing it.

Chronic granulomatous disease is an inborn error of immunity due to disrupted function of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. This results in impaired respiratory burst of phagocytes and insufficient killing of bacteria and fungi. Patients with chronic granulomatous disease are at increased risk for infections, autoinflammation and autoimmunity. Allogeneic hematopoietic stem cell transplantation (HSCT) is the only widely available curative therapy. While HSCT from human leukocyte antigen (HLA) matched siblings or unrelated donors are standard of care, transplantation from HLA-haploidentical donors or gene therapy are considered alternative options. We describe a 14-month-old male with X-linked chronic granulomatous disease who underwent a paternal HLA-haploidentical HSCT using T-cell receptor (TCR) alpha/beta + /CD19 + depleted peripheral blood stem cells followed by mycophenolate graft versus host disease prophylaxis. Decreasing donor fraction of CD3 + T cells was overcome by repeated infusions of donor lymphocytes from the paternal HLA-haploidentical donor. The patient achieved normalized respiratory burst and full donor chimerism. He remained disease-free off any antibiotic prophylaxis for more than three years after HLA-haploidentical HSCT. In patients with x-linked chronic granulomatous disease without a matched donor paternal HLA-haploidentical HSCT is a treatment option worth to consider. Administration of donor lymphocytes can prevent imminent graft failure.

Thickness of the medial orbitofrontal cortex (mOFC) was assessed as it varied with reported symptoms of anxiety and depression in a large sample of anxiety patients. A principal component analysis identified a primary factor of transdiagnostic dimensional distress that predicted 24% of the mOFC variance. Severity of distress symptomology was associated with thinning of the mOFC in both hemispheres for both men and women, regardless of the primary DSM diagnosis. Taken together, the data indicate that mOFC thickness might be useful as an objective measure of disorder severity as well as to assess pharmacological or psychological treatment outcome.

The bioinformational theory of emotional imagery is a model of the hypothetical mental representations activated when people imagine emotionally engaging events, and was initially proposed to guide research and practice in the use of imaginal exposure as a treatment for fear and anxiety (Lang, 1979). In this 50 year overview, we discuss the development of bioinformational theory and its impact on the study of psychophysiology and psychopathology, most importantly assessing its viability and predictions in light of more recent brain-based studies of neural functional activation. Bioinformational theory proposes that narrative imagery, typically cued by language scripts, activates an associative memory network in the brain that includes stimulus (e.g., agents, contexts), semantic (e.g., facts and beliefs) and, most critically for emotion, response information (e.g., autonomic and somatic) that represents relevant real-world coping actions and reactions. Psychophysiological studies in healthy and clinical samples reliably find measurable response output during aversive and appetitive narrative imagery. Neuroimaging studies confirm that emotional imagery is associated with significant activation in motor regions of the brain, as well as in regions implicated in episodic and semantic memory retrieval, supporting the bioinformational view that narrative imagery prompts mental simulation of events that critically includes the actions and reactions engaged in emotional contexts.

Understanding the neural correlates of repetitive retrieval of emotional events is critical in addressing pathological emotional processing, as repeated processing is central for a number of different therapeutic interventions. In the current study, single-trial functional brain activity was assessed in key regions implicated in episodic retrieval, including the medial prefrontal cortex (mPFC), anterior hippocampus, posterior hippocampus, and the posteromedial parietal cortex (i.e., posterior cingulate cortex and the precuneus) following repeated retrieval of pleasant and unpleasant autobiographical events. Replicating previous studies, repetition prompted reduced blood-oxygen-level-dependent (BOLD) amplitude in the anterior hippocampus and the mPFC, but not in the posterior hippocampus, due to no functional activity during mental imagery, or in the posteromedial parietal cortex, due to enhanced activation that was sustained across repetitions. Neural activation during pleasant and unpleasant autobiographical retrieval did not differ as a function of repetition, indicating similar processing effects regardless of motivational relevance. Taken together, the hedonic valence of retrieved memories does not affect functional activity associated with repeated retrieval of episodic events, in which the pattern of BOLD amplitude change suggests a dissociation between the hippocampal-prefrontal circuit, which shows repetition suppression, and the posteromedial parietal cortex, which shows sustained activation.